Hypomethylated Rab27b is a progression-associated prognostic biomarker of glioma regulating MMP-9 to promote invasion

Wang, Hongjun; Wang, Yongzhi; Bao, Zhaoshi; Zhang, Chuanbao; Liu, Yanwei; Cai, Jinquan

doi:10.3892/or.2015.4125

Cited by 16 publications

(14 citation statements)

References 18 publications

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“…Pu et al (23) demonstrated that miR-193a-3p and miR-193a-5p suppressed the metastasis of osteosarcoma cells via inhibition of RAB27B expression. Wang et al (16) reported that high expression of RAB27B was associated with the poor prognosis of patients with glioma, and knockdown of RAB27B significantly inhibited glioma U-87MG Uppsala and LN229 cell invasion, possibly owing to a reduction in matrix metallopeptidase 9 expression and activation. Additionally, Wang et al (16) demonstrated that inhibition of RAB27B expression also reduced the tumor growth in vivo; their data also indicated that RAB27B acts as an oncogene in glioma.…”

Section: Discussionmentioning

confidence: 99%

“…Wang et al (16) reported that high expression of RAB27B was associated with the poor prognosis of patients with glioma, and knockdown of RAB27B significantly inhibited glioma U-87MG Uppsala and LN229 cell invasion, possibly owing to a reduction in matrix metallopeptidase 9 expression and activation. Additionally, Wang et al (16) demonstrated that inhibition of RAB27B expression also reduced the tumor growth in vivo; their data also indicated that RAB27B acts as an oncogene in glioma. The present study determined that overexpression of miR-599 caused a reduction in the expression of RAB27B in U251 cells, which further confirmed that miR-599 could directly bind to RAB27B mRNA and repress its translation.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, RAB27B was determined to be significantly upregulated in ovarian cancer tissues, where it was associated with distant metastasis and poor prognosis (15). Furthermore, patients with high-grade glioma harboring RAB27B hypomethylation or overexpression exhibited a reduced survival time, indicating that the upregulation of RAB27B contributes to glioma progression and poor patient prognosis (16); however, whether miR-599 regulates RAB27B expression in glioma remains unclear.…”

Section: Microrna-599 Suppresses Glioma Progression By Targeting Rab27bmentioning

confidence: 99%

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MicroRNA‑599 suppresses glioma progression by targeting RAB27B

et al. 2018

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MicroRNAs (miRNAs/miRs) serve tumor promoting or suppressive roles in different human cancer types, including glioma; however, the regulatory underlying mechanism by which miR-599 affects glioma progression remains largely unknown. The aim of the present study was to investigate the expression of miR-599 in glioma, as well as the underlying regulatory mechanism. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to examine mRNA and protein expression, respectively. MTT, wound healing and transwell assays were conducted to study cell proliferation, migration and invasion, respectively. A dual-luciferase reporter gene assay was used to confirm the targeting association between miR-599 and Ras-related protein Rab-27B (hereafter RAB27B). In the present study, miR-599 expression was observed to be significantly downregulated in human glioma tissues and cell lines, when compared with normal brain tissues and normal human astrocyte cells, respectively. Low miR-599 expression was significantly associated with glioma progression. Ectopic expression of miR-599 caused a significant reduction in the proliferation, migration and invasion of U-87MG Uppsala and U251 cells. Bioinformatics analysis and dual-luciferase reporter gene assay data identified that RAB27B was a direct target gene of miR-599. The mRNA and protein expression of RAB27B was significantly downregulated following miR-599 overexpression in U-87MG Uppsala and U251 cells. Rescue experiments demonstrated that RAB27B rescued the miR-599-induced inhibition of glioma cell growth, migration and invasion. In addition, RAB27B expression was significantly upregulated in glioma tissues and cell lines, and the expression levels of RAB27B were inversely correlated with miR-599 levels in glioma tissues; therefore, the present study demonstrated that miR-599 exerts a tumor-suppressive role in glioma progression by targeting RAB27B, indicating that miR-599 may be used as a potential candidate for glioma treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Microrna-599 Suppresses Glioma Progression By Targeting Rab27bmentioning

confidence: 99%

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MicroRNA‑599 suppresses glioma progression by targeting RAB27B

et al. 2018

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“…However, there are several limitations in the present study. LN229 is a typical glioma cell line, and when compared with other GBM cells, there are no significant differences in adherence and proliferation capacity (39)(40)(41). However, in the current study, only one GBM cell line was used and there was no verification using animal models.…”

Section: Discussionmentioning

confidence: 88%

Survivin is a prognostic indicator in glioblastoma and may be a target of microRNA‑218

et al. 2019

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Accumulating evidence has revealed that survivin expression is associated with a malignant phenotype and poor prognosis in glioma. Survivin is also a potential target of microRNA (miRNA/miR)-218. The aim of the present study was to investigate the expression and function of survivin in glioblastoma, and to examine the association between survivin and miR-218. For that purpose, survivin mRNA levels were analyzed in 144 frozen samples of glioblastoma using whole-genome RNA sequencing. In vitro cell proliferation, migration, invasion and apoptosis assays were performed, and survivin expression was detected by western blotting. The results revealed that the mRNA expression levels of survivin were negatively and significantly associated with overall survival in glioblastoma. Further in vitro analyses suggested that miR-218 may inhibit the expression of survivin. Expression of miR-218 in the LN229 cell line was significantly lower than that in the immortalized human gliocyte HEB cell line. miR-218 markedly inhibited tumor cell proliferation, migration and invasion capacities, and decreased apoptosis. miR-218 also inhibited the expression of survivin. These results indicated that survivin may be a target of miR-218 and could serve as a predictive biomarker.

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“…Functionally, oncogenes were found to modulate the proliferation, apoptosis and metastasis of glioma cells (24). Moreover, oncogenes were proposed as novel biomarkers and treatment targets for glioma (25). Therefore, elucidating the expression level, clinical significance and biological function of specific oncogene in glioma will greatly contribute to the diagnosis and treatment of glioma.…”

Section: Discussionmentioning

confidence: 99%

B-cell CLL/lymphoma 3 promotes glioma cell proliferation and inhibits apoptosis through the oncogenic STAT3 pathway

Jiang

et al. 2016

International Journal of Oncology

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Aberrant expression of oncogenes and/or tumor suppressors play fundamental roles in the pathogenesis of glioma. B-cell CLL/lymphoma 3 (BCL3) was previously found to be a putative proto-oncogene in human cancers and the decoy receptor DcR1 is induced in a p50/Bcl3-dependent manner and attenuates the efficacy of temozolomide in glioblastoma cells. However, its expression status, clinical significance and biological functions in glioma remain largely unknown. In the present study, the levels of BCL3 were overexpressed in glioma compared to normal brain tissues. Furthermore, high expression of BCL3 protein was confirmed by immunoblotting in glioma cells as compared with normal human astrocyte cell line. The positive expression of BCL3 was correlated with adverse prognostic features and reduced overall survival rate of glioma patients. BCL3 silencing resulted in prominent decreased proliferation, cell cycle arrest in G1 phase and increased apoptosis in U251 cells. In contrast, BCL3 overexpression in U87 cells remarkably facilitated proliferative ability and cell cycle progression and induced apoptosis. In vivo studies showed that BCL3 knockdown inhibited the tumor growth of U251 cells in a mouse xenograft model. Mechanistically, BCL3 positively regulated the abundance of STAT3, p-STAT3 and the downstream targets of STAT3 pathway including BCL2, MCL-1 and cyclin D1 in glioma cells. Furthermore, a positive correlation between BCL3 and STAT3 expression was observed in glioma specimens. Notably, we confirmed that STAT3 knockdown abolished the oncogenic roles of BCL3 in glioma. In conclusion, we suggest that BCL3 serves as an oncogene in glioma by modulating proliferation, cell cycle progression and apoptosis, and its oncogenic effects are mediated by the STAT3 signaling pathway.

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Hypomethylated Rab27b is a progression-associated prognostic biomarker of glioma regulating MMP-9 to promote invasion

Cited by 16 publications

References 18 publications

MicroRNA‑599 suppresses glioma progression by targeting RAB27B

MicroRNA‑599 suppresses glioma progression by targeting RAB27B

Survivin is a prognostic indicator in glioblastoma and may be a target of microRNA‑218

B-cell CLL/lymphoma 3 promotes glioma cell proliferation and inhibits apoptosis through the oncogenic STAT3 pathway

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